U.S. patent number 6,229,142 [Application Number 09/381,774] was granted by the patent office on 2001-05-08 for time of flight mass spectrometer and detector therefor.
This patent grant is currently assigned to Micromass Limited. Invention is credited to Robert H. Bateman, Jonathan C. Cottrell, Anthony J. Gilbert, John B. Hoyes, Thomas O. Merren.
United States Patent |
6,229,142 |
Bateman , et al. |
May 8, 2001 |
Time of flight mass spectrometer and detector therefor
Abstract
An ion detector (27) for use in a time-of-flight mass
spectrometer (1) is disclosed. The ion detector (27), which has an
extended dynamic range, comprises collection electrodes (36, 38;
39) of different surface areas. In one embodiment the collection
electrodes (36, 38; 39) are formed in an array consisting of a
larger plate-like collection electrode (36, 38) and a smaller
plate-like collection electrode (39). Microchannel multiplier
plates (31, 32) may be arranged in front of the collection
electrodes (36, 38; 39). In an alternative embodiment the
collection electrodes consist of a grid (42) or, more preferably, a
wire electrode (50) disposed in front of a plate-like electrode
(43).
Inventors: |
Bateman; Robert H. (Knutsford,
GB), Gilbert; Anthony J. (Chapel-en-le-Frith,
GB), Merren; Thomas O. (Altrincham, GB),
Hoyes; John B. (Stockport, GB), Cottrell; Jonathan
C. (Altrincham, GB) |
Assignee: |
Micromass Limited (Manchester,
GB)
|
Family
ID: |
27451744 |
Appl.
No.: |
09/381,774 |
Filed: |
December 17, 1999 |
PCT
Filed: |
January 25, 1999 |
PCT No.: |
PCT/GB99/00250 |
371
Date: |
December 17, 1999 |
102(e)
Date: |
December 17, 1999 |
PCT
Pub. No.: |
WO99/38191 |
PCT
Pub. Date: |
July 29, 1999 |
Foreign Application Priority Data
|
|
|
|
|
Jan 23, 1998 [GB] |
|
|
9801565 |
Feb 27, 1998 [GB] |
|
|
9804286 |
May 20, 1998 [GB] |
|
|
9810867 |
Jun 18, 1998 [GB] |
|
|
9813224 |
|
Current U.S.
Class: |
250/287;
250/288 |
Current CPC
Class: |
H01J
49/0036 (20130101); H01J 49/025 (20130101); H01J
49/40 (20130101) |
Current International
Class: |
H01J
49/40 (20060101); H01J 49/02 (20060101); H01J
49/34 (20060101); H01J 049/40 () |
Field of
Search: |
;250/288,287,290,292,286 |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
|
|
|
|
|
|
|
2266407 |
|
Oct 1993 |
|
GB |
|
2300513 |
|
Nov 1996 |
|
GB |
|
851549 |
|
Jul 1981 |
|
SU |
|
WO 94/28631 |
|
Dec 1994 |
|
WO |
|
WO 95/00236 |
|
Jan 1995 |
|
WO |
|
WO 98/21742 |
|
May 1998 |
|
WO |
|
Other References
Stephan, Zehnpfenning and Benninghoven, J. of Vac. Sci. Technol. A
1994, vol. 12 (2), pp. 405-410. .
Rockwood et al.,Abstracts, Pittcon 1997, Atlanta, GA, Mar. 1997,
Paper No. 733. .
Kristo and Enke, Rev. Sci. Instrum. 1988, vol. 59, (3), pp.
438-442. .
Cierjacks, Petkovic et al, Nuclear Instrum. And Methods in Physic
Research 1985, vol. A238, pp. 354-364. .
Kellogg, Rev. Sci. Instrum. Jan. 1987, vol. 58 (1), pp.
38-42..
|
Primary Examiner: Arroyo; Teresa M.
Assistant Examiner: Smith, II; Johnnie L.
Attorney, Agent or Firm: Alix, Yale & Ristas, LLP
Parent Case Text
CROSS-REFERENCE TO RELATED APPLICATIONS
This is the national stage of International Application No.
PCT/GB99/00250 filed Jan. 25, 1999.
Claims
What is claimed is:
1. A time-of-flight mass spectrometer (1) comprising:
an ion source (1-24) for repetitively generating bunches of ions
from a sample being analyzed;
ion accelerating means (21) for causing at least some of the ions
comprised in each of said bunches to entering a drift region (24)
along an axis (25) with substantially the same component of kinetic
energy along said axis (25), in which drift region (24) they become
separated in time according to their mass-to-charge ratios;
ion detection means (27) disposed to receive ions after they have
passed through said drift region (24);
means (29,30) for determining the transit time of said ions through
said drift region (24); and
means (29,30) for determining the number of ions having one or more
selected transit times;
characterized in that:
said ion detection means (27) comprises:
at least two collection electrodes (36,38;39), each of which has a
different effective area, and on which said ions or particles
generated from said ions may impinge, each said collection
electrode (36,38;39) having associated therewith separate means
(28) for registering the arrival of a said ion, each said
collection electrode (36,38;39) and its associated means (28) for
registering having a deadtime consequent upon an earlier ion
arrival during which it cannot register another ion arrival;
and
said means (29,30) for determining the number of ions having one or
more selected transit times comprises:
counting means (29,30) for counting the number of ion arrivals
which have been registered at a said selected transit time at one
or more electrodes including the largest of said collection
electrodes (36,38;39) for which the ion arrival rate at that
selected transit time does not exceed a predetermined value above
which the presence of said deadtime would result in significant
errors in the number of ion arrivals registered at that
electrode.
2. A time-of-flight mass spectrometer as claimed in claim 1,
wherein said ion detection means (27) further comprises at least
one charged-particle multiplying means (31,32) for receiving ions
leaving the drift region (24) and for producing a burst of
electrons in response to each ion arriving at said ion detection
means (27) and wherein said collection electrodes (36,38;39) are
arranged to receive electrons comprised in said bursts.
3. A time-of-flight mass spectrometer as claimed in claim 2,
wherein said at least one charged-particle multiplying means
(31,32) comprises a channelplate electron multiplier (31,32).
4. A time-of-flight mass spectrometer as claimed in claim 2,
further comprising a separate conversion electrode, disposed to
receive ions leaving said drift region (24) and to generate
secondary particles for impinging upon said charged-particle
multiplying means (31,32).
5. A time-of-flight mass spectrometer as claimed in claim 1,
wherein said at least two collection electrodes (36,38;39) comprise
two or more plate-like electrodes.
6. A time-of-flight mass spectrometer as claimed in claim 5,
wherein said two or more plate-like electrodes are disposed in the
same plane.
7. A time-of-flight mass spectrometer as claimed in claim 5,
wherein said collection electrodes comprise two collection
electrodes (36,38;39), the larger of said collection electrode
(36,38) having an effective area between 2 and 20 times, that of
the smaller collection electrode (39).
8. A time-of-flight mass spectrometer as claimed in claim 1,
wherein said collection electrodes comprise at least one partially
transparent electrode (42;50) disposed in front of at least one
plate-like electrode (43), wherein said at least one partially
transparent electrode (42;50) intercepts in use a proportion of the
incident ion/electron flux and transmits the remainder to said at
least one plate-like electrode (43).
9. A time-of-flight mass spectrometer as claimed in claim 8,
wherein said at least one partially transparent electrode comprises
at least one grid electrode (42).
10. A time-of-flight mass spectrometer as claimed in claim 8,
wherein said at least one partially transparent electrode comprises
at least one wire electrode (50).
11. A time-of-flight mass spectrometer as claimed in claim 1,
wherein said counting means (29,30) counts in use the number of ion
arrivals which have been registered at a said selected transit time
at:
(a) the largest of said electrodes for which the arrival rate at
that selected transit time does not exceed a predetermined value
above which the presence of said deadtime would result in
significant errors in the numbers of ion arrivals registered at
that electrode; and
(b) at least one electrode smaller than that defined in (a) above,
if present.
12. A time-of-flight mass spectrometer as claimed in claim 1,
wherein the means (28) for registering the arrival of an ion
comprises a fast discriminator (28) which generates a digital
signal whenever the voltage on its associated collection electrode
(36,38;39) rises above a pre-selected level in response to the
arrival of charged particles on the collection electrode
(36,38;39).
13. A time-of-flight mass spectrometer as claimed in claim 12,
wherein said means for determining the transit time of ions through
the drift region (24) comprises a multi-stop time digitizer which
is started when a bunch of ions enter the drift region (24) and
which generates a digital elapsed time signal in response to the
generation of a digital signal from said discriminators (28)
associated with the collection electrodes (36,38;39).
14. A time-of-flight mass spectrometer as claimed in claim 13,
wherein the digital elapsed time signals are stored in a digital
memory together with a flag indicative of which collection
electrode (36,38;39) each signal is associated with.
15. A time-of-flight mass spectrometer as claimed in claim 1,
wherein said counting means (29,30) determines the largest
electrode for which the ion arrival rate at said selected transit
time does not exceed a predetermined value above which the presence
of said deadtime would result in significant errors in the number
of ion arrivals registered at that electrode, by predicting the
ion-arrival rate at the electrodes from a measurement of the
ion-arrival rate at a smaller electrode, and selecting the largest
of said electrodes for which the ion-arrival rate so predicted does
not exceed said predetermined value for that electrode.
16. A time-of-flight mass spectrometer as claimed in claim 1,
wherein said counting means (29,30) determines the largest
electrode for which the ion arrival rate at said selected transit
time does not exceed a predetermined value above which the presence
of said deadtime would result in significant errors in the number
of ion arrivals registered at that electrode, by calculating the
true ion-arrival rate at each electrode using a dead-time
correction algorithm and selecting the largest of said electrodes
for which the ion-arrival rate so calculated does not exceed said
predetermined value for that electrode.
17. A time-of-flight mass spectrometer as claimed in claim 1,
wherein said predetermined value is that value beyond which a
dead-time correction algorithm indicates that correction cannot be
made to a desired degree of accuracy.
18. A time-of-flight mass spectrometer as claimed in claim 1,
wherein said predetermined value is determined by previous
experiment to be the highest ion-arrival rate at which the ratio of
ion counts at that electrode and a smaller electrode remain
substantially constant.
19. A time-of-flight mass spectrometer as claimed in claims 1,
wherein said predetermined value is determined by previous
experiment as being the highest ion-arrival rate at which the ratio
of ion counts at that electrode and a smaller electrode remain
substantially constant after correction of at least the data
associated with the larger electrode using a dead-time correction
algorithm.
20. A method of time-of-flight mass spectrometry comprising the
steps of:
repetitively generating bunches of ions from a sample being
analyzed;
accelerating at least some of the ions comprised in each of said
bunches so that they have substantially the same component of
kinetic energy along an axis (25) and allowing them to separate in
time according to their mass-to-charge ratios during their
subsequent passage through a drift region (24) along said axis
(25);
detecting at least some of said ions after they have passed through
said drift region (24);
determining for each of those ions so detected their transit times
through said drift region (24); and
determining the number of ions having one or more selected transit
times;
said method characterised in that:
the step of detecting at least some of said ions comprises allowing
said ions, or particles generated therefrom, impinging on at least
two collection electrodes (36,38;39) of different effective areas,
each of which having associated therewith separate means (28) for
registering the arrival of a said ion, each said collection
electrode (36,38;39) and its associated means for registering (28)
having a deadtime consequent upon an earlier ion arrival during
which it cannot register another ion arrival; and
the step of determining the number of ions having one or more
selected transit times comprises counting the number of ion
arrivals registered at a said selected transit time at one or more
electrodes including the largest of said collection electrodes
(36,38;39) for which the ion arrival rate at that selected transit
time does not exceed a predetermined value-above which the presence
of said deadtime would result in a significant error in the number
of ions counted.
21. A method of time-of-flight mass spectrometry as claimed in
claim 20, further comprising the step of determining the largest
electrode for which the ion arrival rate at said selected transit
time does not exceed a predetermined value above which the presence
of said deadtime would result in significant errors in the number
of ion arrivals registered at that electrode, by predicting the
ion-arrival rate at the electrodes from a measurement of the
ion-arrival rate at a smaller electrode, and selecting the largest
of said electrodes for which the ion-arrival rate so predicted does
not exceed said predetermined value for that electrode.
22. A method of time-of-flight mass spectrometry as claimed in
claim 20, further comprising the step of determining the largest
electrode for which the ion arrival rate at said selected transit
time does not exceed a predetermined value above which the presence
of said deadtime would result in significant errors in the number
of ion arrivals registered at that electrode, by calculating the
true ion-arrival rate at each electrode using a dead-time
correction algorithm and selecting the largest of said electrodes
for which the ion-arrival rate so calculated does not exceed said
predetermined value for that electrode.
23. A method of time-of-flight mass spectrometry as claimed in
claim 20, wherein said predetermined value is that value beyond
which said dead-time correction algorithm indicates that correction
cannot be made to a desired degree of accuracy.
24. A method of time-of-flight mass spectrometry as claimed in
claim 20, wherein said predetermined value is determined by
previous experiment to be the highest ion-arrival rate at which the
ratio of ion counts at that electrode and a smaller electrode
remain substantially constant.
25. A method of time-of-flight mass spectrometry as claimed in
claim 20, wherein said predetermined value is determined by
previous experiment to be the highest ion-arrival rate at which the
ratio of ion counts at that electrode and a smaller electrode
remain substantially constant after correction of at least the data
associated with the larger electrode using a dead-time correction
algorithm.
Description
BACKGROUND OF THE INVENTION
This invention relates to a time-of-flight mass spectrometer and
its associated ion detection system. It provides apparatus for
detecting ions in a time-of-flight mass spectrometer, and methods
of operating that apparatus, which result in improved performance
at a lower cost when compared with prior spectrometers.
In a time-of-flight mass spectrometer, a bunch of ions enter a
field-free drift region with the same kinetic energy and the ions
temporally separate according to their mass-to-charge ratios
because they travel with different velocities. Ions having
different mass-to-charge ratios therefore arrive at a detector
disposed at the distal end of the drift region at different times,
and their mass-to-charge ratios are determined by measurement of
their transit time through the drift region.
Prior detectors for time-of-flight mass spectrometers comprise an
ion-electron converter followed by an electron multiplying device.
In some embodiments, ions strike a surface of the multiplying
device to release electrons and a separate converter is not
provided. Because the detector must respond to ions leaving the
whole exit aperture of the drift region, it is conventional to use
one or more microchannel plate electron multipliers as the
multiplying device. A collector electrode is disposed to receive
the electrons produced by the channelplates and means are provided
to respond to the current flow so generated and produce an output
signal. The chief difference between such a detector and the
similar device conventionally used with magnetic sector, quadruple
or quadrupole ion-trap spectrometers is the electronic signal
processing, which must produce signals indicative of the transit
time of the ions as well as the number arriving in any particular
time window (corresponding to one or more mass-to-charge ratios).
This data must be generated and read out before the next bunch of
ions can be admitted into the drift region, so that detector speed
is an important determinant of the repetition rate, and hence the
sensitivity, of the entire spectrometer.
The earliest detectors for time-of-flight spectrometers comprised a
DC amplifier connected to the collector electrode and an
analogue-to-digital converter (ADC) for digitizing the output of
the amplifier. Usually, this arrangement was used with time-slice
detection whereby the amplifier was gated to respond only to ions
arriving within a certain time window (typically corresponding to
one mass unit). The time window was moved (relative to the time of
entrance of ions into the drift region) during repeated cycles of
operation so that a complete mass spectrum was eventually recorded.
An improvement involved the use of several amplifiers and ADC's
arranged to simultaneously record a different time window.
Nevertheless, many cycles of the spectrometer are still required to
record a complete mass spectrum and the repetition rate of the
spectrometer is severely limited by the time taken for the
analogue-digital conversion in each cycle. Digital transient
recorders (for example, as described in U.S. Pat. Nos. 4,490,806,
5,428,357 and PCT applications W094/28631 and W095/00236) have been
devised to efficiently process the digital data produced by the
ADC, but, particularly in the case of time-of-flight mass analyzers
for the analysis of organic compounds, these do not represent a
cost-effective solution to the problem of achieving a high
repetition rate.
An alternative detection system for time-of-flight mass
spectrometers is based on ion counting. In these methods, a signal
due to a single ion impact on the detector is converted to a
digital boolean value, "true" (which may be represented by a
digital, "1") in the case of an ion impact, or "false" (e.g, a
digital "0") if there has been no ion impact. Various types of
timers and/or counters are then employed to process the digital
data produced. For example, a counter associated with a particular
time window may be incremented whenever a signal is generated in
that time window. Alternatively, the output of a timer, started
when an ion bunch enters, may be stored in a memory array whenever
the detector generates a "true" signal. The advantage of an
ion-counting detector over an analogue detector is that variations
in the output signal of the electron multiplier due to a single ion
impact, which may be .+-.50% or more, are effectively eliminated
because each signal above the noise threshold is treated
identically. Further, an ion counting detector does not suffer from
the additional noise inevitably produced by the ADC incorporated in
an analogue detector system, and is also taster in operation.
Consequently, the contribution of noise to the overall ion count is
reduced and a more accurate ion count is achieved, particularly in
the case of small numbers of ions. The disadvantage is that the
digital signal representing an ion impact must be processed very
quickly, before the next ion arrives at the detector, it that ion
is to be detected. In practice, all detectors have a "deadtime"
immediately following an ion impact, during which they cannot
respond to an ion impact. This limits the number of ions which can
be detected in a given time, so that a dynamic range of the
detector is also limited. Corrections can be made to the detector
output to compensate for the effects of deadtime (see, for example,
Stephen, Zehnpfenning and Benninghoven, J. Vac. Sci. Technol. A,
1994 vol 12 (2) pp 405-410), and in co-pending European patent
application claiming priority from GB 9801565.4 filed Jan. 23,
1998, but even when such corrections are carried out, the detector
dynamic range still effectively reduces the performance of a
time-of-flight mass spectrometer with such a detector.
An improved ion-counting detector for time-of-flight mass
spectrometry has been described in general terms by Rockwood at the
1997 Pittsburgh Conference, Atlanta, Ga. (paper No 733), and is
available commercially from Sensar Larsen-Davis as the "Simulpulse"
detector. According to information published by Sensar Larson-Davis
it comprises a large number of individual equal-area anodes, each
of which is provided with a digital pulse generating circuit which
is triggered by the arrival of an ion at its associated anode. The
anodes are disposed in a wide-area detector so that they are all
equally likely to be struck by an ion exiting from the drift
region. Consequently, simultaneous (or near-simultaneous) ion
strikes are most likely to occur on different electrodes and the
effect of detector deadtime is greatly reduced. The data from each
of the anodes is summed into an 8-bit digital word representative
of the ion intensity at any particular time, and the value of that
word and its associated time is stored in a digital memory.
However, such a detector is obviously complicated and expensive to
manufacture.
An electron multiplier ion detector for a scanning mass
spectrometer which has two modes of operation to extend its dynamic
range is disclosed by Kristo and Enke in Rev. Sci. Instrum. 1988
vol 59 (3) pp 438-442. This detector comprises two channel type
electron multipliers in series together with an intermediate anode.
The intermediate anode was arranged to intercept approximately 90%
of the electrons leaving the first multiplier and to allow the
remainder to enter the second multiplier. An analogue amplifier was
connected to the intermediate anode, and a discriminator and pulse
counter were connected to an electrode disposed to receive
electrons leaving the second multiplier. The outputs of the
analogue amplifier and pulse counter were electronically combined.
A protection grid was also disposed between the multipliers. At
high incident ion fluxes, the output signal comprised the output of
the analogue amplifier connected to the intermediate anode. Under
these conditions a potential was applied to the protection grid to
prevent electrons entering the second multiplier (which might of
otherwise cause damage to the second multiplier). At low ion
fluxes, the potential on the protecting grid was turned off and the
output signal comprised the output of the pulse counter. In this
mode the detector operated in the single ion counting mode. In this
way the detector was operable in a low sensitivity analogue mode
using the intermediate anode and a high sensitivity ion counting
mode using both multipliers and the pulse counter, so that the
dynamic range was considerably greater than a conventional detector
which only uses one of these modes.
Other prior art teaching of electron multipliers with means for
extending the dynamic range includes a simultaneous mode (i.e.,
pulse counting and analogue) electron multiplier taught in U.S.
Pat. No. 5,463,219. U.S. Pat. No. 4,691,160 teaches a discrete
dynode electron multiplier having two final collector electrodes of
different areas, each connected to a separate analogue amplifier
and selectable by means of a manually operated switch. Soviet
Inventors Certificate SU 851549 teaches the disposition of a
control grid between two channelplate electron multipliers, the
potential on which can be adjusted to control the gain of the
assembly. GB patent application 2300513 teaches a similar control
grid disposed between certain dynode sheets in an electron
multiplier comprising a stack of such sheets, and which is
especially suitable for a photomultiplier tube. Prior art disclosed
in U.S. Pat. No. 4,691,160 also comprises a continuous dynode
electron multiplier having two collector electrodes, one of which
is capable of receiving electrons from a dynode disposed prior to
the final dynode so that the multiplier has less gain.
Multiple anode detectors have also been used in time-of-flight mass
spectrometers for imaging the spatial distribution of ions leaving
the drift region, usually in conjunction with imaging
time-of-flight analyzers. Such position-sensitive detectors are
taught by Cierjacks, Petkovic et al. in Nucl. Instrum. and Methods
in Phys. Res., 1985 vol A238 pp 354-364, Kellogg in Rev. Sci.
Intrum. 1987 vol 58 (1) pp 38-42 and in PCT application No.
WO87/00682. These detectors produce signals indicative of the
spatial co-ordinates of an ion impact and operate in a
substantially different way from the multiple-anode "Simulpulse"
detector. They are generally slow in operation and use analogue
signal processing rather than the ion-counting principle employed
in the present invention.
SUMMARY OF THE INVENTION
It is an object of the present invention to provide a
time-of-flight mass spectrometer and a detector therefor, which has
a greater dynamic range than most prior apparatus and which is
cheaper to manufacture than prior spectrometers and detectors of
equivalent performance. It is a further object to provide methods
for operating such a spectrometer and detector.
According to a first aspect of the present invention there is
provided a time-of-flight mass spectrometer.
The term, "effective area" should be taken to mean the area of that
part of a collection electrode on which the ions or other particles
may impinge, corrected as necessary for any lack of uniformity in
the spatial distribution of ions incident on said ion detection
means.
Preferably, the ion detection means further comprises
charged-particle multiplying means which receives the ions leaving
the drift region and produces a burst of electrons in response to
each ion arriving at the detection means. In such a case, the
collection electrodes are disposed to receive these electrons.
Typically, one or more channelplate electron multipliers may be
used.
A separate conversion electrode, disposed to receive ions leaving
the drift region and to generate secondary particles which then
enter a particle multiplying means, may also be provided.
The collection electrodes may conveniently comprise two or more
plate-like electrodes of different effective areas disposed in the
same plane.
Alternatively, they may comprise one or more partially transparent
electrodes disposed in front of one or more plate-like electrodes
so that the partially transparent electrode(s) intercept a
proportion of the incident ion/electron flux and transmit the
remainder to the plate-like electrodes behind them.
A suitable partially transparent electrode may comprise a grid
electrode, in which the case the ratio of the effective areas of
the grid electrode and a plate-like electrode will be determined by
the transmission efficiency of the grid.
More preferably, however, the partially transparent electrodes may
comprise a single wire. It has been found in practice that the
effective area of a thin single-wire electrode disposed between a
plate-like electrode and the electron multiplier plates is
considerably greater than its actual area.
In preferred embodiments, said means for determining the number of
ions having one or more selected transit times comprises means for
counting the number of ion arrivals which have been registered
at:
(a) The largest of said electrodes for which the arrival rate at
that selected transit time does not exceed a predetermined value
above which the presence of said deadtime would result in
significant errors in the numbers of ion arrivals registered at
that electrode, and
(b) At least one electrode smaller than that defined in (a) above,
if present.
In preferred embodiments, the means for registering the arrival of
an ion may comprise a fast discriminator which generates a digital,
"true" signal whenever the voltage on its associated collector
electrode rises above a pre-selected threshold level in response to
the arrival of charged particles on the electrode.
Means for determining the transit time of ions through the drift
region may comprise a multi-stop time digitizer which is started
when a bunch of ions enters the drift region and which generates a
digital elapsed time signal in response to the generation of a
"true" signal from the discriminators associated with the
collection electrodes.
The elapsed time signals may then be stored in a digital memory
together with a flag indicative of which collector electrode each
signal is associated with.
In further preferred embodiments, two collector electrodes are
provided, the larger one having an effective area between 2 and 20
times, and most preferably about 8 times, that of the smaller.
Means for counting the ion arrivals registered at each of said
selected transit times may comprise a suitably programmed digital
computer. Conveniently, clock pulses corresponding to each of the
selected transit times are generated and at each clock pulse each
means for registering an ion arrival is interrogated. In the case
that an ion arrival is registered during a given clock pulse, the
digital representation of the transit time from the time digitizer
is stored in memory, together with a flag indicative of which
electrode the arrival was at. The time digitizer may be reset on
the generation of a new ion bunch so that the arrivals of ions in
different bunches with a given mass-to-charge ratio are recorded
with equivalent transit times. Alternatively, the time at which
each ion bunch is generated may be stored along with the ion
arrival times so that actual transit times can be calculated later
by subtraction of the start time of the ion bunch with which each
arrival time is associated. At the end of a series of ion bunches,
the total number of ions arriving at each of the collection
electrodes at one or more (typically all) selected transit times
may then be computed.
Digital computing means may also be used to estimate the ion
arrival rate at each collection electrode and to establish whether
or not it exceeds a predetermined value.
Unfortunately, a decision on whether data from the second
collection electrode is reliable at any given transit time cannot
be made directly on the basis of the observed ion arrival rate at
that electrode because the observed rate may be affected by
deadtime. For example, the observed rate may fall to zero in the
case of an extending deadtime detector subject to a high ion
arrival rate.
A preferred method of estimating the ion arrival rate at an
electrode is to count the number of ion arrivals at the smallest
electrode at each of said selected transit times. If these are less
than a predetermined value, then the ion arrival rate at the
largest electrode at that transit time may be regarded as being
sufficiently low to avoid deadtime problems. Consequently, data
from the larger electrode may be used to determine the number of
ions having that selected transit time. However, if the number of
ion arrivals at the smaller electrode exceeds the predetermined
value, data associated with the larger electrode is likely to be
inaccurate and the number of ions having that transit time should
be determined from the data associated with the smaller electrode
only. The predetermined value may be established by determining the
ratio of the ion counts at both electrodes at different incident
ion fluxes. This ratio will remain constant as the flux is
increased up to the point at which deadtime effects begin to affect
the data associated with the larger electrode. At that point, the
ratio will become biased in favour of the smaller electrode and the
predetermined value may be established accordingly.
Alternatively, in a less preferred embodiment, the ion arrival rate
may be estimated by implication from the ratio of the number of
bunches in which an ion arrival is registered at a given transit
time to the total number of ion bunches. Should this ratio exceed a
predetermined value (established from a consideration of the known
detector deadtime relative to the frequency of the generation of
the ion bunches), data associated with the largest electrode may be
rejected and use should be made only of data associated with the
next smaller electrode. The ion arrival rate at the smaller
electrode will obviously be less than that at the larger electrode
(in proportion to the ratio of the effective areas of the
electrodes), so that the loss of counts due to ions arriving during
its deadtime will be correspondingly smaller. Count data associated
with the smaller electrode is then typically employed in preference
to that associated with the larger electrode for subsequent transit
times until the ion arrival rate at the larger electrode has fallen
to an acceptable level. Care must be taken in the case of detectors
having extending deadtimes that the lack of ion counts due to
complete saturation of the larger electrode is not mistaken for a
reduction in the true ion arrival rate, typically by inspection of
the count data of the smaller electrodes, which in these
circumstances will indicate ion arrivals while none are being
registered at the larger electrode.
Alternatively, data associated with the second collection electrode
may be corrected step-by-step for the effects of deadtime, starting
at the beginning of a peak. The magnitude of the correction so
generated may then indicate that the ion arrival rate at the
electrode later in the peak would be so great that adequate
correction would be impossible, in which case data from the first
collection electrode alone should be used to characterise the
entire peak.
This method has the advantage that more accurate counts can be
obtained for an ion arrival rate which is not so high as to require
a switch to data associated with a smaller electrode but is high
enough to result in some losses due to deadtime.
A further preferred embodiment comprises use of the method of
deadtime correction taught in co-pending PCT patent application No.
PCT/GB99/00251 filed Jan. 25, 1999 which requires that the raw
count data from the largest electrode is first processed by
conventional mass spectrometric data handling software to produce
an uncorrected mass spectrum which is subsequently corrected for
the effects of deadtime by means of a previously calculated look-up
table.
In the method of that application, the data acquired is processed
to produce at least one observed mass spectrum comprising data
representing the number of ions having particular transit times,
and to recognize in the mass spectrum portions of the data which
correspond to mass peaks. The process determines from at least one
of said portions of data an observed peak area and an observed mass
centroid; uses a predetermined peak shape function characteristic
of said time-of-flight mass spectrometer and selected according to
said observed mass centroid, to determine from said observed mass
centroid a distribution function indicative of the shape of said
mass peak; and applies a correction to said observed mass centroid
to obtain a value of said mass centroid corrected for the effect of
detector dead-time, said correction being obtained from a
predetermined correction table which gives values of said
correction for different values of said distribution function and
said observed peak areas, said predetermined table having been
obtained by predicting the effect of said detector dead-time on
each of a plurality of simulated mass peaks having said peak-shape
functions for appropriate ranges of said distribution functions and
peak areas.
The digital computing means is further programmed to multiply the
data associated with the smaller electrode by a factor based on the
ratio of the effective areas of the electrodes to make the data
associated with that electrode comparable with that associated with
the larger electrode.
The invention extends the dynamic range of the spectrometer because
in prior single-collector electrode spectrometers, the ion flux has
to be limited to prevent saturation of the detector, otherwise data
is irretrievably lost, even if prior methods of deadtime correction
are applied. In a spectrometer according to the invention, the
ion-flux can be increased beyond that which would cause saturation
of the largest collector, thereby allowing low intensity peaks to
be recorded using data associated with the largest electrode, while
the most intense peaks may be recorded using data associated with
the smaller electrodes. A similar result is achieved by the prior
"Simulpulse" detector discussed above, but the present invention,
using electrodes of different effective areas represents a more
cost-effective solution by reducing the number of electrodes and
their associated electronics. In the invention, the dynamic range
may be increased by approximately a factor of 10 by the use of two
electrodes having a ratio of areas of 10:1 while a similar increase
using the prior detector would require 10 electrodes of equal
areas.
It will be appreciated that the invention is particularly valuable
when the spectrometer comprises an ion source which is capable of
producing intense ion beams at certain masses and far smaller ion
beams at other masses, for example an inductively-coupled plasma
ion source or electron-impact, chemical ionization or APCI ion
sources. However, other types of ion sources, for example
electrospray or matrix-assisted laser desorption ion sources
(MALDI) may also be employed.
According to a second aspect of the present invention there is
provided a method of time-of-flight mass spectrometry.
Preferred variations on the method will be apparent from the
discussion presented above in respect of the apparatus of the
invention.
BRIEF DESCRIPTION OF THE DRAWINGS
Various embodiments of the present invention will now be described,
by way of example only, and with reference to the accompanying
drawings in which:
FIG. 1 is a schematic drawing of an ICP mass spectrometer;
FIG. 2 is a drawing of an ion detector;
FIG. 3 is a drawing of a collector electrode array suitable for use
in the detector of FIG. 2;
FIG. 4 is a drawing of an alternative ion detector; and
FIG. 5 is a sectional view in the plane AA shown in FIG. 4.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
Referring first to FIG. 1, an ICP mass spectrometer generally
indicated by 1 comprises an ICP torch 2 which generates a plasma 3.
As in conventional ICP mass spectrometers a sample to be analyzed
may be introduced into the torch 2 entrained in the torch gas
supplies (not shown). Ions characteristic of such a sample are
generated in the plasma 3. The torch 2 is disposed adjacent to a
sampling cone 4 which comprises an orifice 5 through which at least
some of the ions generated in the plasma 3 may enter a first
evacuated chamber 6 which is pumped by a first pump 7. In agreement
with conventional practice there is provided a skimmer 8 which
cooperates with the sampling cone 4 to provide a nozzle-skimmer
interface. An additional stage of pumping is provided by a second
pump 10 connected to a second evacuated chamber 9. Ions from the
plasma 3 exit from the skimmer 8 along an axis 11, pass through the
second evacuated chamber 9 and exit through a third evacuated
chamber 13 through an orifice in a conical extraction lens 12 which
forms part of the boundary wall between the chambers 9 and 13. The
third chamber 13 is evacuated by a third pump 14. In accordance
with the teachings of EP patent application 0813228 a hexapole rod
assembly 15 (containing gas at a pressure of about 10.sup.-2 torr)
is provided in the third evacuated chamber 13 to reduce
interferences from unwanted species and reduce the energy spread of
ions.
After passing through the rod assembly 15 ions pass through an
orifice 16 in a wall 17 which divides the third evacuated chamber
13 from a fourth evacuated chamber 18 which contains a
time-of-flight mass analyzer. A vacuum pump 19 maintains the
pressure in the chamber 18 at 10.sup.-6 torr or better. On entering
the evacuated chamber 18 the ions pass through an electrostatic
focusing lens 20 and enter an ion pusher 21, electrodes in which
are fed with pulses from a pulse generator 22 in such a way that
bunches of ions are repeatedly ejected parallel to an axis 25 into
a drift region 24. In a general sense, therefore, items 1-24
comprise an ion source for repeatedly generating bunches of ions.
The ion pusher 21 comprises ion accelerating means for causing at
least some of these bunches to enter the drift region with
substantially the same component of kinetic energy along the axis
25 (which is perpendicular to the ion axis 11). This arrangement
therefore comprises an orthogonal acceleration time-of-flight
analyzer, but a linear arrangement is also within the scope of the
invention. The ions leaving the ion pusher 21 travel into the drift
region 24 along a trajectory 23, (which deviates from the axis 25
because the ions have a finite component of velocity in the
direction of the ion axis 11), and become separated in time
according to their mass to charge ratios. The drift region 24 is a
reflecting type analyzer and comprises an electrostatic ion mirror
26 which changes the direction of travel of the ions following
trajectory 23 and directs them into an ion detector 27. Use of the
ion mirror 26 both decreases the size of the spectrometer and
improves mass resolution but a linear analyzer could be used if
desired. Means for registering the arrival of a said ion comprises
at least two fast discriminators 28 (one for each of the electrodes
in the ion detector 27) and produces a digital signal each time an
ion arrives at the detector 27. Means for determining the transit
time of ions through the drift region 24, and means for determining
the number of ions having one or more selected travel times
comprise a clock generator 29 and a digital computer 30 and are
described in more detail below.
Referring next to FIG. 2, an embodiment of the ion detector 27
suitable for use in the invention comprises first and second
microchannel multiplier plates 31 and 32 disposed to receive ions
directed towards the detector 27 by the ion mirror 26 (FIG. 1).
This ion flux is schematically illustrated in FIG. 2 by the arrows
33. Each ion strikes the front surface of the first multiplier
plate 31 causing the release of a burst of electrons at its rear
surface at a point corresponding to the ion impact. These electrons
are received at the front face of the second multiplier plate 32 so
that a larger burst of electrons is generated at its rear face.
These impact on a collection electrode array 34 and the charge so
transferred to one or more of the electrodes in the array is
detected by the discriminators 28. A power supply 35 maintains
potential differences between the faces of the multiplier plates 31
and 32, as required for their proper operation.
A collection electrode array suitable for use in the invention is
illustrated in FIG. 3. It comprises an insulated substrate 37,
typically of ceramic, on which are coated three electrically
conductive electrodes 38, 39 and 36. Two of these, electrodes 38
and 36, are connected by the lead 41 and function as a single
electrode of area approximately eight times that of the smaller
electrode 39. This arrangement of electrodes compensates for an
inhomogeneous distribution of the ion flux represented by the array
33, at least along an axis parallel to the long dimension of the
electrode 39, but of her arrangements of electrodes are within the
scope of the invention.
It will be appreciated that the arrival of the ions at the detector
27 is random in space (in the absence of any instrumentally
introduced inhomogeneity) so that the number of ion arrivals
recorded at the composite larger electrode comprising electrodes 38
and 36 will be according to the preferred embodiment approximately
eight times that recorded on the smaller electrode 39. In this
invention the detector is not position sensitive and, given a
homogeneous ion flux, the only significance of the pattern of the
electrodes is the ratio of their areas. It, however, in any
practical embodiment the ion flux is known to be inhomogeneous, the
electrode pattern can be arranged to minimize its effect.
An alternative ion detector is illustrated in FIG. 4. It comprises
an insulated substrate 44 on which is coated a plate-like electrode
43. Electrode 43 is connected by a lead 45 to one of the
discriminators 28. A grid electrode 42 is supported by insulators
47 and 48 between the exit face of the multiplier plate 32 and the
plate-like electrode 43. The grid electrode 43 has a transparency
such that it intercepts approximately 12.5% of the electrons
leaving the multiplier plate 32 and transmits the remainder to the
plate-like electrode 43. A lead 46 connects the grid electrode 42
to another of the discriminators 28.
A disadvantage of the ion detector shown in FIG. 4 is that the
effective area of the grid electrode is strongly dependent on the
threshold setting of the discriminator 28. For the grid electrode
the amplitude of the current pulses produced extends over a greater
range than those produced by the plate-like electrode 43,
presumably because electrons passing close to the wires comprising
the grid but not actually striking a wire induce a signal in the
electrode which is smaller than the minimum signal which would be
produced by impact of those electrons on a solid electrode. This
effect becomes more pronounced as the number of wires comprised in
the grid is increased. While it has the effect of allowing the
effective area of the grid to be varied by adjusting the threshold
of the discriminator 28, it is more difficult to maintain the ratio
of the effective areas of the grid electrode 42 and the plate
electrode 43 at a constant value. Consequently, in a more preferred
embodiment of the ion detector the grid electrode 42 (FIG. 4) may
be replaced by a single wire 50 stretched across the electrode 43
between the insulators 47 and 48. FIG. 5 is a sectional view in the
direction of the ion flux 33 in the plane AA shown in FIG. 4 and
shows such an arrangement. Typically a wire 0.5 mm diameter can be
used. The range of pulse amplitudes produced by such an electrode
is smaller than that produced by a grid electrode but still greater
than that produced by the plate electrode, which provides adequate
stability of the ratio of the effective areas while allowing some
adjustment of that ratio by alteration of the threshold level of
the discriminator 28. Because of this "induction" effect the
effective area of the wire 50 is considerably greater than its
actual area.
A power supply 49 is arranged to bias positively the inputs of the
discriminators 28 relative to the exit face of the multiplier plate
32 so that electrons leaving it are accelerated towards the grid
electrode 42 and the plate-like electrode 43. In this embodiment
the larger electrode comprises the plate-like electrode 43 which
has an effective area approximately 8 times that of the smaller
electrode which comprises the grid electrode 42. However, a more
accurate value of the ratio of the effective areas can be
established by monitoring the signals from both electrodes
simultaneously.
As explained above, although two electrodes are adequate for most
purposes, it is also within the scope of the invention to use a
greater number, each of which has a different area. Further,
particularly in the event of inhomogeneity of the incident ion
beam, the effective areas of the electrodes may not be exactly
equivalent to their actual areas. The ratio of the effective areas
may be easily established, however, by monitoring the signals from
both electrodes while the detector is receiving a substantially
constant ion flux, for example from a calibration compound
introduced into the ion source. Care must be taken, however, that
the ion intensity during the calibration process is not so great
that the signal from the larger electrode is distorted by detector
dead-time.
Each electrode comprised in the array is connected to a fast
discriminator 28 which responds to the arrival of charge at an
electrode by generating a digital signal comprising a flag and a
time value obtained from a clock pulse generator 29 at the moment
the arrival of charge is detected. A digital computer 30 stores
this value so that the transit time of the ion which generated the
signal can be determined. To facilitate this, the time at which the
ion pusher 21 is activated by the pulse generator, thereby causing
a bunch of ions to enter the drift region, is also stored by the
computer 30. The transit time of each detected ion is determined
merely by subtracting the appropriate time of entry of the ions
into the drift region from the time at which the ion is detected,
using a digital computer 30.
The computer 30 is programmed to determine the number of ions
having one or more transit times as follows:
First, the number of times an ion arrival is registered at each of
the electrodes at each tick of the clock pulse generator 29, is
determined by inspection of the flagged transit time data, so that
a histogram of ion counts against transit time (which corresponds
to a mass spectrum uncorrected for dead-time) may be produced in
respect of each electrode. In the event that only certain mass
peaks need to be monitored, ion count data need only be retained at
each of one or more selected transit times (i.e., clock ticks)
corresponding to the mass-to-charge ratios to be monitored.
Next, the ion arrival rate at the smallest collection electrode 39
is compared with a predetermined value (typically established by
experiment, as explained previously) to establish whether or not
data from the composite largest electrode (38,36) is acceptable. If
it is, the sum of the counts on both the largest electrode and the
smallest electrode is used to determine the number of ions having
that particular transit time. If the comparison indicates that data
associated with the larger electrode is likely to be inaccurate,
only data associated with the smaller electrode 39 is used,
multiplied by a factor dependent on the ratio of the effective
areas of the electrodes. This process is repeated for each of the
selected transit times.
An alternative method of estimating the ion arrival rate is the
application of a prior method of deadtime corrections to the raw
count data at each selected transit time, such as that discussed by
Stephan (see above). The point at which the ion arrival rate
becomes high enough for the significant deadtime corrections to be
necessary will then be obvious from the results of the correction
process. If corrections are applied to the count data then a higher
predetermined value for the ion arrival rate can be used to trigger
the switch to a smaller electrode because the corrections applied
will result in more reliable data being produced for the larger
electrodes at high arrival rates. However, use of most prior
methods of deadtime correction incurs significant computing time,
thereby reducing the repetition rate of the spectrometer, or
requires storage of a large volume of data in high-speed memory.
Another method of applying some deadtime correction is to process
the uncorrected count data using conventional mass-spectrometric
data processing software to recognise the mass peaks and produce a
"stick" mass spectrum comprising values of ion intensity for each
recognised mass peak using data obtained on one or more electrodes
including the largest one. This data may then be corrected for
deadtime according to the method of a co-pending International
Application No. PCT/GB99/00251 filed Jan. 25, 1999. This will
indicate regions of the spectrum where the ion arrival rate is high
enough to require only the use of data associated with the smaller
electrode, and those portions of the spectrum may then be replaced
by equivalent portions obtained by an identical treatment of the
ion count data obtained on the smaller electrode, allowing for the
ratio of the effective areas of the electrodes.
* * * * *